Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy

被引：2055

作者：

Yu, TaChung ^{[1
]}

Guo, Fangfang ^{[1
]}

Yu, Yanan ^{[1
]}

Sun, Tiantian ^{[1
]}

Ma, Dan ^{[1
]}

Han, Jixuan ^{[1
]}

Qian, Yun ^{[1
]}

Kryczek, Ilona ^{[2
]}

Sun, Danfeng ^{[1
,2
]}

Nagarsheth, Nisha ^{[2
]}

Chen, Yingxuan ^{[1
]}

Chen, Haoyan ^{[1
]}

Hong, Jie ^{[1
]}

Zou, Weiping ^{[2
]}

Fang, Jing-Yuan ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes,Shanghai, Key Lab Gastroenterol & Hepatol,Shanghai Canc Ins, Minist Hlth,Div Gastroenterol & Hepatol,Renji Hos, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China

[2] Univ Michigan, Ctr Comprehens Canc, Grad Programs Immunol & Canc Biol, Dept Surg,Sch Med, Ann Arbor, MI 48109 USA

来源：

CELL | 2017年 / 170卷 / 03期

基金：

中国国家自然科学基金;

关键词：

RESISTANCE; CELLS; COMMENSAL; OXALIPLATIN; SENSITIVITY; STATISTICS; MECHANISMS; MICROBIOTA; EXPRESSION; CETUXIMAB;

D O I：

10.1016/j.cell.2017.07.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum orchestrates a molecular network of the Toll-like receptor, microRNAs, and autophagy to clinically, biologically, and mechanistically control colorectal cancer chemoresistance. Measuring and targeting F. nucleatum and its associated pathway will yield valuable insight into clinical management and may ameliorate colorectal cancer patient outcomes.

引用

页码：548 / +

页数：32

共 47 条

[1]

Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc [J].